A time course investigation of the statin paradox among valvular interstitial cell phenotypes

Abstract

Monzack EL, Masters KS. A time course investigation of the statin paradox among valvular interstitial cell phenotypes.

Valve Interstitial Cells: The Key to Understanding the Pathophysiology of Heart Valve Calcification

“…6 A recent study by Monzack and colleagues showed that in porcine VICs treated with osteogenic medium or under reduced serum conditions (where the cells expressed high levels of aSMA), statins actually increased ALP activity and the expression of osteocalcin. 65 Statins are now the front line in prevention of atherosclerosis, but the present conclusion is that they have no effect in preventing aortic valve calcification. Possibly the statins might inhibit development in healthy valves, but once the calcification process has started, the statins cannot stop it.…”

“…Male VICs have higher expression of genes responsible for proliferation and apoptosis; functional implications are confirmed by cell behavior in culture 65 Monzack, 2012 Porcine Time-dependent response of VICs to growth, myofibroblast and osteogenic medium Cells in osteogenic medium have increased alkaline phosphatase activity, high proliferation, downregulation of aSMA. 66…”

Robust Generation of Quiescent Porcine Valvular Interstitial Cell Cultures

“…The importance of using the correct VIC phenotype will become increasingly important as these models transition from tools for basic research and discovery to drug testing applications; for example, multiple studies have reported that statin drugs elicit differential responses in aVICs versus osteoblastic VICs. 41,42 Careful evaluation not only of the biochemical and physical cues present in each model but also of the starting phenotype of the VICs under study will be necessary to mimic healthy and diseased valve behavior and to reliably predict biological responses to pharmacological treatments.…”

Simvastatin Does Not Diminish the In Vivo Degeneration of Decellularized Aortic Conduits

“…Without pro-calcific feeding, decellularized aortic conduit grafts exhibited only microcalcification or sparse hydroxyapatite islets in the media after 8 weeks in the same heterotopic graft implantation model. 26,27 Moreover, enhanced calcium deposition was reported to stabilize atherosclerotic plaques and to lower the rate of major adverse cardiovascular events. 25 However, under the experimentally induced severely pro-calcific metabolic conditions, statin treatment could not decrease the calcium deposition or the gene expression of several markers of chondro-osteogenic transformation in the implants along this study.…”